[Molecular-genetic characteristics of Mycobacterium tuberculosis strains isolated from patients with tuberculous spondylitis].

AIM: Molecular-genetic characteristic of M. tuberculosis strains isolated from operation material of patients with tuberculous spondylitis. MATERIALS AND METHODS: 107 strains of M. tuberculosis isolated in 2007 - 2011 from patients with spine tuberculosis were studied by methods of spoligotyping and MIRU-VNTR by 12 and 24 loci. RESULTS: Strains of genetic family Beijing dominated (n = 80), 78% of those had multiple drug resistance (MDR). Strains of genetic families T, H3 (Ural), LAM, Manu, H4 and S were also detected. Differentiating of 80 strains of Beijing genotype by MIRU-VNTR method by 24 loci revealed 24 variants (HGI = 0.83) including 7 clusters, the largest of those (100-32) included 23 strains (87% MDR). CONCLUSION: The leading role of Beijing genotype M. tuberculosis strains in development of tuberculous spondylitis with multiple drug resistance of the causative agent is shown.

Interactions between gut inflammation and arthritis/spondylitis.

PURPOSE OF REVIEW: The spectrum of spondyloarthritis is characterized by the intriguing co-occurrence of gut and joint inflammation, although no obvious anatomical link exists. RECENT FINDINGS: Data from animal models identify stromal cells as important players in pathogenesis, although signalling through TNFRI appeared to be sufficient for development of combined gut and joint inflammation. Interleukin-23 receptor was identified as a susceptibility locus for ankylosing spondylitis. SUMMARY: Human genome studies combined with animal model research provide us with new evidence in the fascinating field of the gut-joint axis. However, how these newly identified genetic associations can influence the immunological environment remains to be elucidated.

Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men.

According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.

[Genetics in patients with psoriatic arthritis]. / Arthritis psoriaticaában szenvedo betegek genetikai vizsgálata.

OBJECTIVES: HLA antigens were studied in 100 Hungarian patients suffered from psoriatic arthritis. Genetic markers for the development of different clinical pattern of the disease and skin disorder were identified. METHODS: Determination of class I and class II antigens was performed by using microlymphocytotoxicity assay. RESULTS: The frequency of HLA-Cw6, HLA-B16 (and its split B-39) and HLA-B27 antigens were significantly higher in psoriatic arthritis patients than in the Hungarian general population. No connection was found between HLA-DR4, DR7, B17 antigens and psoriatic arthritis. The patients were classified according to the subgroups proposed by Gladman. The comparisons between the clinical subgroups revealed a significant association of HLA-B27 with spondylitis (Gladman 4, 5, 6, 7). There was no association between HLA DR4 and polyarticular pattern of the disease (Gladman 3, 7). Psoriasis seemed to be significantly associated only with HLA-Cw6. There was a higher frequency of HLA-B38 in psoriatic arthritis patients with erythroderma.

Clinical and immunogenetic characterization in psoriatic arthritis patients.

In psoriatic arthritis (PsA), genetic factors play a substantial role in disease susceptibility as well as in its expression. This study aims to determine the distribution of class I and class II HLA antigens in PsA patients and secondly to analyze the influence of genetic factors in the clinical expression of the disease. Consecutive PsA patients (CASPAR criteria) with less than 1 year of disease duration were included. Sociodemographic and clinical data were recorded. Blood samples were obtained, DNA was extracted by polymerase chain reaction (PCR), and class I (A, B, and C) and class II (DR) HLA antigens were determined by oligotyping. A control group of 100 nonrelated healthy controls from the general population served as control. p values were corrected (pc) according to the number of alleles tested. A total of 73 patients were included, 37 were females (50.7 %) with a median disease duration of 72 months (interquartile range (IQR) 24-149). Thirty-three patients (45.2 %) had a family history of psoriasis. When analyzing all the class I and class II HLA antigens, a significantly higher frequency of B38 (odds ratio (OR) 2.95, p = 0.03) and Cw6 (OR 2.78, p = 0.009) was found in PsA patients compared to the control group. On the contrary, the HLA-A11 (OR 0.14, p = 0.04) and B7 (OR 0.31, p = 0.03) were significantly more frequent among healthy controls. Furthermore, B18 was significantly more frequent in patients with early arthritis onset (less than 40 years): seven patients (22.6 %) with early onset compared to two patients (4.8 %) with late onset (p = 0.03). No association between HLA-B27 and spondylitis or HLA-DR4 with polyarticular involvement was observed. The HLA-B38 and Cw6 alleles are associated with a greater PsA susceptibility in Argentine population.

[Significance of intestinal inflammation in the pathogenesis of spondylarthropathies]. / Betekenis van darminflammatie in de pathogenese van de spondylarthropathieen.

The concept of spondylarthropathy (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, the urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteria, and since the gut is implied in different forms of spondylarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondylarthropathies by performing ileo-colonoscopies. In the first ileo-colonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly not presenting any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileo-colonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileo-colonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondylarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileo-colonoscopied patients were reviewed 2 to 9 years later:about 6% of SpA patients not presenting any sign of Crohn's disease at first investigation but demonstrating gut inflammation on biopsy, developed full-blown Crohn's disease. By performing electronmicroscopy it was described that in patients with SpA the number of membranous (M) cells, which are scarce in normal ileum, is increased in number in inflamed mucosa. They showed a thin rim of cytoplasm covering groups of lymphocytes. In chronic inflammatory lesions necrotic M-cells, rupture of M-cells and lymphocytes entering the gut lumen was observed. The bursting of M-cells at the top of the lymphoid follicles leads to interruption of the gut epithelial lining and gives the luminal content access to the lymphoid tissue. This can be responsible for an exponential increase of local antigen stimulation. Accelerated luminal antigen presentation through a break in the epithelial layer, together with cytokines released from activated monocytes, might induce a second line of defense aiming at elimination of the massive antigen penetration into the mucosa. The postulated switch from secretory local immunity to a systemic type of local immune reaction could have different consequences:the local down-regulation of J chain in the IgA immunocytes could shift the production of polymeric IgA to monomers, jeopardizing secretory immunity; the disproportionate increase of IgG-producing cells could favor further inflammation and tissue damage through complement activation and arming of the killer cells, and cause autoimmune responses locally and in target organs at a distance (e.g. joint organs). The discovery of subclinical gut inflammation in the SpA had therapeutic consequences. Sulphasalazine (SASP) has been proven to be an active drug in the treatment of IBD. Since the gut could play a crucial role in SpA, it was logic to use this drug in the treatment of this disease. Multiple open and double-blind studies have proven the effectiveness of this drug in SpA.

[Rheumatic pelvic spondylitis in a patient with progressive spinal muscular atrophy (Kugelberg-Welander syndrome)]. / Pelvi spondilite reumatica in soggetto con atrofia muscolare spinale progressiva (s. di Kugelberg-Welander).

A unique association of two rare genetic diseases--progressive muscular atrophy of the spine and rheumatic pelvic spondylitis--observed in a clinical case is described.

Nineteen-year-old female with unilateral ankle pain. What is your diagnosis?

The case history of a 19-year-old female with left ankle pain of 18 months' duration is presented. The reader is encouraged to make his or her own diagnosis after reviewing the history, laboratory values, and imaging. The final diagnosis with a full explanation and differential diagnosis will follow.

[Chronic osteitis and arthritis of palmoplantar pustulosis. A familial form of B-27 negative spondylarthropathy]. / Les ostéites et arthrites chroniques de la pustulose palmo-plantaire. Une forme familiale de spondylarthropathie B27 négative.

A 35-year old woman presented with pustulosis palmaris et plantaris evolving in acute episodes parallel to those of a rheumatic disease consisting of bilateral sacro-iliac arthritis, manubriosternal fusion and sterno-clavicular arthritis. Her brother had spondylitis compatible with the diagnosis of pustular osteo-arthritis though without pustulosis. He presented with bilateral sacro-iliac arthritis, manubriosternal fusion, sterno-clavicular arthritis and an ossified fragment detached from the antero-inferior angle of C6. The two patients had the same HLA phenotype: A1, A9, B5, B41, CW4, DR2, DR4, absence of B27. In a specimen from the sacro-iliac joint the authors found active bone remodelling and inflammatory osteitis with fibrosis and infiltrates rich in mononucleate cells. An electron microscopic study--to the authors' knowledge, the first to be performed in such cases--demonstrated intracytoplasmic filamentous inclusions in two macrophages of the synovial fringe. Only one other case of the familial form has been published so far. Like the rheumatism of acne conglobata, the spondylitis of pustulosis palmaris et plantaris is one of the causes of sterno-costo-clavicular hyperostosis.

[Prognostic factors in early inflammatory arthritis]. / Les facteurs de pronostic des rhumatismes inflammatoires au début de la maladie.

Rheumatoid arthritis (RA) and spondylarthropathies are the most frequent chronic inflammatory arthritides. RA is a potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the first clinical symptoms. However RA is a heterogenous disorder characterized by wide variations in clinical manifestations, disease course and response to therapy. No prognosis factor has been identified and universally accepted and validated. Markers of prognosis would be highly appreciated by clinicians who could then more closely adapt their management decisions to the disease potential. Clinical and biological data collected to date have provided a limited amount of information. Nevertheless, ESR, CRP and rheumatoid factor titer appeared to be the most powerful available indicators of prognosis at the early stage of the disease. Recent progress in molecular biology strongly suggests that genetic markers (HLA-DRB1 alleles) could be correlated with disease severity and it would appear possible to distinguish immunogenetically homogeneous subpopulations of patients with RA. Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover could correlate to rate of joint destruction. Finally a combination of the most pertinent markers could determine a "score of severity" of the disease. In spondylarthropathies, limited information is available at present. The variables which were usually correlated with disease severity are: onset before 16 years of age, hip arthritis, ESR, limitation of lumbar spine, sausage-like finger or toe, oligoarthritis, poor efficacy of nonsteroidal antiinflammatory drugs and rapid evolution during the first 2 years. Genetic factors could also have prognosis value that should be clarified.

[Fluctuating asymmetry as a marker of phenotypic adaptiveness (modelled on the neurological manifestations of lumbar osteochondrosis]. / Fluktuiruiushchaia asimmetriia kak marker adaptivnosti fenotipa (na modeli nevrologicheskikh proiavlenii poiasnichnogo osteokhondroza).

Analysis of palm ridge count a-b was carried out in 217 males having neurological expressions of lumbar osteochondrosis and 300 control persons. Higher indices of fluctuating asymmetry have been recorded in the group of patients thus suggesting a low stability of development. It was proposed that fluctuating asymmetry can mark phenotypes weakly adapted to postnatal environmental effects.

[Seronegative spondylarthropathies--an overview]. / Seronegative Spondarthritiden--eine Ubersicht.

The seronegative spondyloarthropathies are a group of mostly chronic diseases sharing many clinical, radiologic, and genetic features. Described are the main characteristics of the different subsets. Growing evidence of new disease associations will lend new impulses to research of pathogenesis.

Spondyloarthropathy in Caucasians and non-Caucasians.

The striking association between the spondyloarthropathies and HLA-B27 transcends all ethnic and geographical boundaries. The relationship between the various entities is well defined for many conditions, but others such as pustulotic arthroosteitis, undifferentiated spondyloarthropathy, and seronegative enthesopathic arthropathy of childhood are less clear. The association between B-27 and disease is less dramatic in non-Caucasians where cross-reacting antigens and other genetic determinants may be more important. Worldwide, some 20% of individuals develop sacroiliitis or Reiter's syndrome following an unknown or specific infective agent, respectively. The debate continues as to whether B27 itself is operative or whether additional gene or genes are required. Detailed epidemiological and molecular analysis is required.

Geoepidemiology: the environment and spondyloarthropathies.

Spondyloarthropathies (SPA) are a group of common inflammatory rheumatic disorders characterized by axial and or peripheral arthritis, associated with enthesitis, dactylitis and potential extra-articular manifestations such as uveitis and skin rash. The diseases which comprise the group, share a common genetic predisposition, the HLA-B27 gene, however this association varies markedly among the various SPAs and among different ethnic groups. Environmental factors seem to be triggering the diseases in the genetically predisposed. The radiographic hallmark of the group is sacroiliitis, which when present is of help in the diagnosis. Various sets of diagnostic and classification criteria were developed over the years with the latest European Spondyloarthropathy Study Group (ESSG) criteria which are the most widely used. MRI changes have been included in the new classification criteria of early axial SPA and are now considered as a major tool in the diagnosis. Until recent years, there were no real disease modifying anti-rheumatic drugs which were able to halt the disease progression. Tumor necrosis factor (TNF)-alfa blocking agents, have now become the mainstream of therapy providing the patients an effective treatment option.